alexa Efficient and cost effective population resequencing by pooling and in-solution hybridization.
Clinical Research

Clinical Research

Journal of Clinical Research & Bioethics

Author(s): Bansal V, Tewhey R, Leproust EM, Schork NJ

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Abstract High-throughput sequencing of targeted genomic loci in large populations is an effective approach for evaluating the contribution of rare variants to disease risk. We evaluated the feasibility of using in-solution hybridization-based target capture on pooled DNA samples to enable cost-efficient population sequencing studies. For this, we performed pooled sequencing of 100 HapMap samples across ∼ 600 kb of DNA sequence using the Illumina GAIIx. Using our accurate variant calling method for pooled sequence data, we were able to not only identify single nucleotide variants with a low false discovery rate (<1\%) but also accurately detect short insertion/deletion variants. In addition, with sufficient coverage per individual in each pool (30-fold) we detected 97.2\% of the total variants and 93.6\% of variants below 5\% in frequency. Finally, allele frequencies for single nucleotide variants (SNVs) estimated from the pooled data and the HapMap genotype data were tightly correlated (correlation coefficient > = 0.995).
This article was published in PLoS One and referenced in Journal of Clinical Research & Bioethics

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